Experimental work on heparin has indicated that its half-life increases with dose. Two models to describe heparin's pharmacokinetic behavior are proposed, and the parameters in the models are fitted to experimental data. Both models exhibit an apparent firstorder decay with a “halflife” that increases with dose. It is shown that, even though both models exhibit a bolus half-life of from 1 to 2 hr, over 2 days can be required for true steadystate conditions to be achieved in these models when a constant intravenous infusion of drug is given. The clinical implications of these models are discussed. Suggestions are made for further research on heparin kinetics.
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This work was supported in part by the National Institutes of Health under Grant RR 0704811. The work was also supported in part by U.S. Government Grants MB 00146 and GM 23826, which were made to the Laboratory of Applied Pharmacokinetics at the University of Southern California, School of Medicine.
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McAvoy, T.J. Pharmacokinetic modeling of heparin and its clinical implications. Journal of Pharmacokinetics and Biopharmaceutics 7, 331–354 (1979). https://doi.org/10.1007/BF01062533
- metabolite-inhibition model